阿来替尼对比化疗用于克唑替尼治疗后进展的间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌：来自 III 期 ALUR 研究的结果。

Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.

机构信息

Department of Oncology, University of Turin, Turin, Italy.

Department of Pneumology, Toulouse University Hospital, Paul Sabatier University, Toulouse, France.

出版信息

Ann Oncol. 2018 Jun 1;29(6):1409-1416. doi: 10.1093/annonc/mdy121.

DOI:10.1093/annonc/mdy121

PMID:29668860

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6005013/

Abstract

BACKGROUND

This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib.

PATIENTS AND METHODS

ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS).

RESULTS

Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4 months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks).

CONCLUSION

Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02604342; Roche study MO29750.

摘要

背景

这是首个直接比较艾乐替尼与标准化疗在克唑替尼治疗后进展或不耐受的晚期/转移性间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）患者中的疗效和安全性的试验。

患者和方法

ALUR（MO29750；NCT02604342）是一项随机、多中心、开放性、III 期艾乐替尼对比化疗治疗既往接受过铂类双联化疗和克唑替尼治疗的晚期/转移性 ALK 阳性 NSCLC 患者的研究。患者按 2:1 随机分配接受艾乐替尼 600mg 每日 2 次或化疗（培美曲塞 500mg/m2 或多西他赛 75mg/m2，每 3 周一次），直至疾病进展、死亡或退出。主要终点为研究者评估的无进展生存期（PFS）。

结果

共有 107 名患者在欧洲和亚洲的 13 个国家/地区被随机分配（艾乐替尼组 n=72；化疗组 n=35）。艾乐替尼组的中位研究者评估 PFS 为 9.6 个月[95%置信区间（CI）：6.9-12.2]，化疗组为 1.4 个月[95%CI：1.3-1.6]（风险比（HR）0.15[95%CI：0.08-0.29]；P<0.001）。独立审查委员会评估的 PFS 也明显更长，艾乐替尼组为[HR 0.32（95%CI：0.17-0.59）；中位 PFS 为 7.1 个月（95%CI：6.3-10.8），化疗组为 1.6 个月（95%CI：1.3-4.1）]。在基线有可测量中枢神经系统（CNS）疾病的患者（艾乐替尼组 n=24；化疗组 n=16）中，艾乐替尼组的 CNS 客观缓解率显著高于化疗组（54.2%对 0%；P<0.001）。化疗组发生≥3 级不良事件（AE）的比例（41.2%）明显高于艾乐替尼组（27.1%）。尽管艾乐替尼治疗持续时间更长（20.1 周对 6.0 周），但因 AE 而停药的发生率较低（5.7%对 8.8%）。